title: mTOR regulates phagosome and entotic vacuole fission.
abstract: Macroendocytic vacuoles formed by phagocytosis, or the live-cell engulfment program entosis, undergo sequential steps of maturation, leading to the fusion of lysosomes that digest internalized cargo. After cargo digestion, nutrients must be exported to the cytosol, and vacuole membranes must be processed by mechanisms that remain poorly defined. Here we find that phagosomes and entotic vacuoles undergo a late maturation step characterized by fission, which redistributes vacuolar contents into lysosomal networks. Vacuole fission is regulated by the serine/threonine protein kinase mammalian target of rapamycin complex 1 (mTORC1), which localizes to vacuole membranes surrounding engulfed cells. Degrading engulfed cells supply engulfing cells with amino acids that are used in translation, and rescue cell survival and mTORC1 activity in starved macrophages and tumor cells. These data identify a late stage of phagocytosis and entosis that involves processing of large vacuoles by mTOR-regulated membrane fission.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 BCMB Allied Program, Weill Cornell Medical College, New York, NY 10065.
authors.forename: Matej
authors.initials: M
authors.lastname: Krajcovic
authors.forename: Shefali
authors.initials: S
authors.lastname: Krishna
authors.forename: Leila
authors.initials: L
authors.lastname: Akkari
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Joyce
authors.forename: Michael
authors.initials: M
authors.lastname: Overholtzer
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D057691:Entosis; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D008954:Models, Biological; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D058570:TOR Serine-Threonine Kinases